Over 0.5 million Americans per year die following cerebral ischemic- anoxic insults (cardiac arrest, asphyxia, hypoxemia). 20 percent or more of survivors have permanent brain damage. Post-ischemic changes may impair and new therapy may improve neurologic recovery. Although recent studies have shown EEG and metabolic recovery of neurons after up to 60 min. of ischemia, their relation to long-term functional neurologic recovery has not yet been established. We have recently developed a long-term (7 days) monkey model of reversible isolated total brain ischemia of 16 min. (neck tourniquet occlusion and other features) which includes post-ischemic intensive care and results in survival with predictable severe neurologic deficit (stupor, coma). It permits correlation of physiologic, neurologic and neuropathologic changes. Circulatory, respiratory, metabolic and acid-base variables are controlled. The objective of this study is to elucidate with this model (a) the pathogenesis and time course of post-ischemic-anoxic encephalopathy; and (b) promising therapy (hemodilution, increased perfusion pressure, osmotherapy, hypothermia, steroid, combinatton of above). Although these therapies seem beneficial from acute studies, their ability to improve functional neurologic recovery ("quality of life") has not been proven. In series (1) (minimal monitoring) we will correlate changes in EEG, intracranial pressure and neurologic function (quantitative) with histopathology on 7th day; in control and 6 therapy groups. In Series (2) (intensive monitoring) we will study in addition cerebral blood flow (luxury perfusion, "no reflow") and metabolism (long-term changes in CMRO2 and CMRG). In a separate group (survival beyond 7 days) we will search for objective criteria of irreversibility (e.g. declining CMRO2). The results of these studies will help in selection and application of therapies not yet in use.